Stent with a bio-resorbable connector

ABSTRACT

A helical stent having bio-resorbable connecting members connecting sections of the stent. The connecting members provide various spring rates or spring constants to the stent, and permit a change in the flexibility of the stent subsequent to implantation while maintaining the unitary design of the stent.

PRIORITY

This application is a continuation of U.S. patent application Ser. No.12/096,902, now U.S. Pat. No. 7,862,607, which is a U.S. national stageapplication under 35 USC §371 of International Application No.PCT/US2006/062479, filed Dec. 21, 2006, which claims benefit of priorityto U.S. Provisional Patent Application No. 60/755,330, filed Dec. 30,2005, each of which is incorporated by reference in its entirety intothis application.

BACKGROUND

It is known in the medical field to utilize an implantable prosthesis tosupport a duct or vessel in a mammalian body. One such prosthesis mayinclude a frame-like structure. Such frame-like structures are commonlyknown as a “stent”, “stent-graft” or “covered stent.” For the purpose ofdiscussion, these structures are referred to collectively herein as a“stent.”

The stent can be utilized to support a duct or vessel in the mammalianbody that suffers from an abnormal widening (e.g., an aneurysm, vesselcontraction or lesion such as a stenosis or occlusion), or an abnormalnarrowing (e.g., a stricture). Stents are also utilized widely in theurethra, esophagus, biliary tract, intestines, arteries, veins, as wellas peripheral vessels. The stent can be delivered via a small incisionon a host body. Hence, the use of stents as a minimally invasivesurgical procedure has become widely accepted.

The stents can be cut from a tube or wound from a wire on a mandrel.Thereafter, the stents can be expanded in the duct or vessel of a hostby a separate mechanism (e.g., balloon) or by utilization of a materialthat self-expands upon predetermined implantation conditions.

One common form of the stent is configured as a series of essentiallyidentical rings connected together to form a lattice-like framework thatdefines a cylindrical or tubular framework. The series of rings may ormay not have connecting linkages between the adjacent rings. One exampledoes not utilize any connecting linkages between adjacent rings as itrelies upon a direct connection from one ring to the next ring. It isbelieved that more popular examples utilize connecting linkages betweenadjacent rings, which can be seen in stent products offered by variouscompanies in the marketplace.

All of the above stent examples utilize a biocompatible metal alloy(e.g., Nitinol or Elgiloy). The most common metal alloy utilized bythese examples is Nitinol which has strong shape memory characteristicsso that Nitinol self-expand when placed in the duct or vessel of amammalian body at normal body temperature. In addition toself-expansion, these stents utilize a series of circular rings placedadjacent to each other to maintain an appropriate longitudinal spacingbetween each rings. These stents are also intended to be a permanentimplant in that removal subsequent to implantation requires majorinvasive surgery.

Recently, however, stents are being investigated for use in a host as atemporary implant by having the stents degrade or absorbed by the hostbody. The primary advantage of such temporary stents is the eliminationof additional surgery to remove the stent after it has served itsfunction of dilating a lesion or stenosis in the vessel or duct. Theentire stent is believed to be resorbed by the host body after a periodof time after implantation.

More recently, a combination of the features of the permanent stent andthe bio-resorbable stent are also known. For example, U.S. PatentPublication No. US 2005/0222671 (published Oct. 6, 2005) shows anddescribes a series of connected annular rings with some of theconnectors being biodegradable over time. U.S. Pat. No. 6,258,117 showsand describes at least a series of rings made from a biocompatiblematerial (e.g., metal alloys) connected to each other via breakable orbiodegradable links or connectors.

It is believed that these examples of partially biodegradable stentspresent a potential problem in that once the connecting linkages havebiodegraded, the separated or unjoined annular rings could besusceptible to migration in the host body. It is believed that in asituation where the connector linkages have degraded faster than tissueincorporation (e.g., endothialization) of the annular rings, the ringscould have the ability to migrate away from the original implantationsite. Where the stent is a covered stent (i.e., a stent-graft), it isalso believed that migration of discrete sections of the stent-graftcould occur.

There is thus a need for an implantable prosthesis device that maintainsthe patency of a vessel with little or no ability to migrate from theimplantation site while maintaining the patency of the duct or vessel ofthe host.

BRIEF SUMMARY OF THE INVENTION

Accordingly, the present invention relates to an implantable medicaldevice that has various spring rates or spring constant to permit achange in the flexibility of the stent subsequent to implantation whilemaintain various components of the device unitary which tends toalleviate a potential problem for stent migration for the known stents.

One embodiment includes a stent that includes a plurality of arcuatesections and at least one connector. The plurality of arcuate sectionscircumscribes a longitudinal axis from a first portion to a secondportion to define essentially a portion of a tube. The arcuate sectionsare spaced apart along the longitudinal axis to form at least onecontinuous helical path about the longitudinal axis. The at least oneconnector is arranged to connect one arcuate section to an adjacentaxially spaced arcuate section. The at least one connector is made froma material that is bioresorbed upon exposure to biological tissue suchthat the stent has a first spring constant in an unimplanted conditionand a second different spring constant in an implanted condition after apredetermined period of time.

A further embodiment includes a method of deploying a stent. The methodcan be achieved by providing a stent having at least a portion of thestent bio-resorbable or biodegradable, the stent having a first springconstant; and changing the first spring constant of the stent to asecond helical spring constant different than the first upon exposure tobiological materials.

Another embodiment includes a stent. The stent can be in theconfiguration of a helical that includes a plurality of arcuate sectionsand at least one connector between adjacent arcuate sections. Theplurality of arcuate sections circumscribes a longitudinal axis from afirst portion to a second portion to define essentially a portion of atube. The arcuate sections are spaced apart along the longitudinal axisto form at least one continuous helical path about the longitudinalaxis. The at least one connector connects one arcuate section to anadjacent arcuate section and configured to be absorbed upon exposure tobiological tissue.

Yet another embodiment includes a method of making a stent. The methodcan be achieved by forming a plurality of openings through acircumferential surface of a generally tubular member; filling each ofthe openings with a bio-resorbable member to provide for a continuouscircumferential surface of the tubular member; and removing materialsfrom the circumference of the generally tubular member to define aplurality of struts.

These and other embodiments, features and advantages will becomeapparent to those skilled in the art when taken with reference to thefollowing more detailed description of the invention in conjunction withthe accompanying drawings that are first briefly described.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are incorporated herein and constitutepart of this specification, illustrate exemplary embodiments of theinvention, and, together with the general description given above andthe detailed description given below, serve to explain the features ofthe invention.

FIG. 1 illustrates an embodiment of the helical stent in a perspectiveview.

FIG. 2 is a side view of the structure of the stent of FIG. 1.

FIG. 3A is a close-up side view of a connector disposed between twohelical struts of FIG. 1.

FIG. 3B is a variation of the connector illustrated in FIG. 3A.

FIG. 3C is another variation of the connector illustrated in FIG. 3A.

FIG. 4 illustrates the stent structure of a variation of the embodimentof FIG. 1.

FIGS. 5A-5D illustrate graphically the process of making the stent ofFIG. 1.

FIG. 6 illustrates a variation of the stent structure of the embodimentof FIG. 1.

FIG. 7 illustrates a potential problem with a known stent.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The following detailed description should be read with reference to thedrawings, in which like elements in different drawings are identicallynumbered. The drawings, which are not necessarily to scale, depictselected embodiments and are not intended to limit the scope of theinvention. The detailed description illustrates by way of example, notby way of limitation, the principles of the invention. This descriptionwill clearly enable one skilled in the art to make and use theinvention, and describes several embodiments, adaptations, variations,alternatives and uses of the invention, including what is presentlybelieved to be the best mode of carrying out the invention.

As used herein, the terms “about” or “approximately” for any numericalvalues or ranges indicate a suitable dimensional tolerance that allowsthe part or collection of components to function for its intendedpurpose as described herein. Also, as used herein, the terms “patient”,“host” and “subject” refer to any human or animal subject and are notintended to limit the systems or methods to human use, although use ofthe subject invention in a human patient represents a preferredembodiment.

FIGS. 1-6 are graphical representations of the preferred embodiments.

FIG. 1 illustrates a preferred embodiment of the helical stent 100 in aperspective view. The stent defines a generally cylindrical structureabout a longitudinal axis A₀-A₁. To aid the viewer in visualization ofthe helical path 10 about the axis A₀-A₁ as defined by the zig-zagstruts 12 of the stent 100, the helical path 10 is illustrated as twodashed lines generally circumscribing about the axis A₀-A₁, having afirst end A₀ and a second end A₁. To further aid visualization, thestent 100 illustrated in FIGS. 1 and 2 displays only the foregroundstructure of the stent 100, with the background structure (such as thestruts 12 continuing along the helical path 10 in the background) notdisplayed or only symbolically illustrated. It is noted that where theapplication of a covered stent is desired, the path 10 is also arepresentation of another embodiment where the struts 12 are covered(partially or wholly) by a suitable material (e.g., ePTFE, Dacron,Nylon, fibrin, to name a few).

The zig-zag struts 12 can be simplified to a repeating pattern of twostruts, a strut S1 and a strut S2. A first strut pair Z1 of the strutsS1 and S2 define a first apex A1 extending towards the first end A₀.When the first strut pair Z1 is coupled to a second strut pair Z2 ofstruts, having struts S3 and S4 and defining a second apex A3, the pointwhere the first strut pair Z1 is connected to the second strut pair Z2defines a connecting apex A2 extending away from the first end A₀. Aplurality of strut pairs of Z1 and Z2 can be coupled and located on thehelical path 10 as the path generally circumscribes the axis A₀-Ai.Although the strut pair Z1 is shown as generally identical to the strutpair Z2, each of the strut pairs can be of a different configuration.For example, the struts S1-S4 may be identical in the central portion ofthe stent and different proximate the ends of the stent and vice versa(e.g., different in the central portion and identical proximate the endsof the stent).

In circumscribing and translating along the axis, the helical path 10follows a portion of a complete circle while at the same timetranslating along the axis A₀-A₁. As such, a plurality of arcuatesections AS (labeled as AS₁, AS₂, AS₃, AS₄, and AS₅ in FIG. 2) definedby the successive pairing of strut pairs Z1 and Z2 circumscribes theaxis A₀-Ai from a terminal first end to a terminal second end of thehelical path 10, to thereby define essentially a portion of a tube asillustrated in FIG. 1. The arcuate sections AS are spaced apart alongthe axis A₀-Ai to form at least one continuous helical path 10 about theaxis A₀-A₁. As illustrated in FIG. 2, each of the arcuate sections ASform an angle with respect to the axis A₀-A₁ to define a respectivehelical angle θ with respect to a plane L intersecting and orthogonal tothe axis A₀-A₁. The helical angle θ can be different for each arcuatesection AS. Two or more helical segments, made of one or more arcuatesections AS, can be provided with different geometries by coupling onearcuate section AS2 having one helical angle θ₁ and another arcuatesection AS4 having another helical angle θ₂ different from the onehelical angle θ₁, as illustrated in FIG. 2.

The strut pairs Z1 and Z2 of each arcuate section AS are expandable andprovide radial expandability to the arcuate section AS such that theplurality of arcuate sections AS have an unexpanded insertion size(FIGS. 5C-5D) and a larger expanded size (FIGS. 1-4 and 6) uponimplantation. The expanded arcuate sections AS include a plurality ofstruts S1-S4 that extend in different directions with respect to thedirection of the axis A₀-A₁.

Each of the arcuate sections AS may be connected to adjacent arcuatesections AS via a link or connector 20. In the preferred embodiments,the connector 20 couples the apex of a strut pair on one arcuate sectionto the apex of another strut pair on another arcuate section. At leastone connector 20 is configured to be absorbed upon exposure tobiological tissue.

Details of such connection between arcuate sections AS are illustratedand described in FIGS. 3A-3C. In FIG. 3A, the connector 20A is agenerally linear connector that extends from the connecting apex A2 (oras close as technically feasible from the apex or outermost surface ofthe intersection of struts S2 and S3) to the first apex A1. Theconnector 20A is oriented at an angle α with respect to the axis A₀-A₁.When the stent illustrated in FIG. 3A is superimposed on a planarviewing surface, the apices A1 and A2 are offset at a circumferentialdistance CS and a longitudinal distance LS. The struts S1-S4 of thestrut pairs Z1 and Z2 can be connected directly to each other asillustrated in FIG. 2 or coupled together via a curved intermediatemember IS, illustrated as intermediate member IS1 and intermediatemember IS2 in FIG. 3A. The curved intermediate member IS can include anysuitable curve as long as the curved intermediate member IS functions toreduce stress concentration that can be generated when two generallylinear members (struts S1-S4 as illustrated in FIG. 2) are connecteddirectly to each other. In the preferred embodiments, the curved memberIS have a radius with a curvature R, with a curvature R1 for the firstapex A1 and a curvature R2 for the connecting apex A2 as illustrated inFIG. 3A. Curvatures R1 and R2, and curvature R3 (not shown), for secondapex A3, can generally be equal different from each other.

In FIG. 3B, the connector 20B is formed of three generally linearsegments LS1, LS2, and LS3 such that the connector extends in threedirections that are each not oblique to the direction of the axis A₀-A₁.Because of the three linear shapes of the linear segments LS1, LS2, andLS3, there is no curvilinear segment provided as a connector 20.Depending on the offset of the apices A1 and A2 to each othercircumferentially and longitudinally, the length of linear segments LS2and LS3 may be different from each other or zero for one or both. InFIG. 3C, however, a curvilinear connector 20C can be utilized. The widthW1 of the connector 20C can be the same as the width W2 of the strut S2.Depending on the application of the helical stent 100, the width of thestruts S1-S4 may be 50% larger or smaller than the width W1 of theconnector 20. The width W3 of the intermediate member IS can be largerthan the width W2 of the struts S1-S4 in order to control expansion ofthe helical stent 100.

Instead of the zig-zag strut pair Z1-Z2 shapes shown in FIG. 2, thehelical stent 100 may have plurality of struts arranged as a pluralityof undulations U (labeled as U1, U2, U3, U4, and U₅ in FIG. 4) disposedon the continuous helical path 10 of FIG. 1. The helical path 10 isformed by a plurality of arcuate sections AS (labeled as AS1-AS5 in FIG.4) about the axis A₀-A₁ where the plurality of undulations U includes apeak P and a trough T arranged between three individual struts ST1, ST2,and ST3, for example. In this alternate variation of the helical stent100, there is at least one connector 20 connecting one of theundulations U to an adjacent undulation U.

The undulations U can be wave-like in pattern. The wave-like pattern canalso be generally sinusoidal in that the pattern may have the generalform of a sine wave, whether or not such wave can be defined by amathematical function. Alternatively, any wave-like forms can beemployed so long as it has amplitude and displacement. For example, asquare wave, saw tooth wave, or any applicable wave-like pattern definedby the struts where the struts have substantially equal lengths orunequal lengths.

The connector 20 can connect any portion of the undulations U but it ispreferred that the peaks P and troughs T of one arcuate section AS areconnected to the peaks P and troughs T of an adjacent arcuate sectionAS, which are spaced apart along the axis A₀-A₁. In the most preferredembodiment, at least one connector 20 connects a peak P of one arcuatesection AS to a peak P of an adjacent arcuate section AS where the peaksP are offset circumferentially with respect to the axis A₀-A₁. Where thepeaks P are not offset, the connector 20 extends substantially parallelwith respect to the axis A₀-A₁ of the helical stent 100. As noted above,however, it is most preferred that at least one connector 20 extendsobliquely with respect to a direction extending parallel to the axisA₀-A₁. The connector 20, for example, can also be configured to connectone peak P of one arcuate section AS4 to a trough T of another arcuatesection AS5 as indicated by connector 22 in FIG. 4, which is oblique tothe direction of the axis A₀-A₁. The connector 20 can also be from thepeak P of one section AS4 to the trough of another section AS5 via aconnector 24 that is generally parallel to the direction of the axisA₀-A₁. Moreover, at least one connector 20 is configured to be absorbedupon exposure to biological tissue.

There are variations for the connectors 20 in the helical stent 100illustrated in FIG. 4 that are worthy of further discussion. One type ofconnector is generally similar to the connector 20A illustrated in FIG.3A while variations of the connector 20A are delineated as 20A1, 20A2,20A3, 20A4, 20A5, and 20A6 in FIG. 4. A wave like connector 20C1 canalso be utilized along with a curvilinear connector 20D1. The connectorsmay be arranged in a repeating pattern or they may be arranged in anon-repeating pattern in the helical stent 100. In the preferredembodiment, the number of struts S1-S4 disposed above and belowconnectors 20 (between sequential connectors 20 connecting arcuatesections AS) can be the same. For example, as illustrated in FIG. 4 byarcuate section AS3 which includes repeating undulations IB (each havingtwo struts and a loop 30) that are helically wound along and about theaxis A₀-A₁. There are preferably nine undulations U in eachcircumferential winding or arcuate section AS1-AS5 and the undulations Uare interdigitated. With reference to arcuate sections AS2-AS4, aconnector 20 is located every three undulations therebetween, and eachconnector 20 extending from arcuate section AS3 joins undulations U onthe adjacent arcuate sections AS2 and AS4, which are one and one-halfpitches away (or three struts over from directly across, as illustratedby the struts identified as ST1-ST3 of the arcuate section AS3 betweenthe connector 20A4 and the connector 20D1). All connectors 20 in thecentral portion AS3 of the helical stent 100 preferably extend in thesame direction, longitudinally crosswise across the helical spacebetween adjacent arcuate sections AS. This preferred exemplar embodimentprovides a very symmetrical distribution of connectors 20 in at leastthe longitudinal middle of the helical stent 100. In particular,referring to FIG. 4, in an area 35 which is a space bounded by portionsof AS2 and AS3 and by connectors 20A3 and 20A4, tracing a path from anyone connector disposed on the A₀-facing side of AS3 (e.g., connector20A4) to the nearest connector on the A₁-facing side of AS3 (e.g.,connector 20D1) and counting struts disposed between the connectors 20,there are counted three struts (identified as ST1-ST3 in FIG. 4).Likewise, traveling from any one connector (e.g., connector 20A3) to thenext connector (e.g., connector 20D1) in an opposite direction aroundarea 35 also traverses exactly three struts (identified as ST6, ST5, andST4 in FIG. 4). It is believed that a design having equal number strutsbetween connectors as defined herein provides advantageouscharacteristics with regard to flexibility and strength. In thepreferred embodiment, the number of struts in the clockwise orcounterclockwise direction around an area (an area 35 for example) canrange from 3 to 7. Alternatively, the number of struts in one directioncan be different from the number of struts in the other direction. Forexample, in section AS3, the number of struts between connector 20A3 andconnector 20C1 (in a counter-clockwise direction) is one whereas thenumber of struts between connector 20A6 to connector 20A4 is five (in aclockwise direction).

In one preferred embodiment, about 20% to about 80% of the total numberof connectors 20 for the helical stent 100 are bio-resorbable. Inanother preferred embodiment, all of the connectors 20 arebio-resorbable.

One suitable bio-resorbable material for the connector 20 can be one ormore of a metal alloy shown and described in U.S. Pat. No. 6,287,332 orthe metal alloy shown and described in U.S. Patent ApplicationPublication No. 2002/0004060, which are incorporated by reference intheir entirety. Preferably, the metallic bioabsorbable material isselected from a first group consisting essentially of: magnesium,titanium, zirconium, niobium, tantalum, zinc, silicon, and combinationsthereof. Also provided are mixtures and alloys of metallic bioabsorbablematerials, including those selected from the first group. Various alloysof the materials in the first group can also be used as a metallicbioabsorbable material, such as a zinc-titanium alloy, for example, asdescribed in U.S. Pat. No. 6,287,332 to Bolz et al. The physicalproperties of the alloy can be controlled by selecting the metallicbioabsorbable material, or forming alloys of two or more metallicbioabsorbable materials. For example, the percentage by weight oftitanium can be in the range of about 0.1% to about 1%, which can reducethe brittle quality of crystalline zinc. Without being bound to theory,it is believed that the addition of titanium leads to the formation of aZn₁₅Ti phase. In another embodiment, gold can be added to thezinc-titanium alloy at a percentage by weight of about 0.1% to about 2%,which is believed to result in a further reduction of the grain sizewhen the material cures and further improving the tensile strength ofthe material.

In some embodiments, the metallic bioabsorbable material can be an alloyof materials from the first group and a material selected from a secondgroup consisting essentially of: lithium, sodium, potassium, calcium,iron, manganese, and combinations thereof. The metallic bioabsorbablematerial from the first group can form a protective oxide or passivationcoating upon exposure to blood or interstitial fluid. The material fromthe second group is preferably soluble in blood or interstitial fluid topromote the dissolution of the oxide coating. Also provided are mixturesand alloys of metallic bioabsorbable materials, including those selectedfrom the second group and combinations of materials from the first groupand the second group.

Briefly, the combination of metal materials can be a metal alloy, theselection of the alloy constituents serving to attain the prerequisiteof biocompatible decomposition. Consequently, the metal alloy mayconsist of a combination of material that will decompose in the bodycomparatively rapidly while forming harmless constituents. Such alloymay include a component A which covers itself with a protective oxidecoating. This component A is selected from one or several metals of thegroup of magnesium, titanium, zirconium, niobium, tantalum, zinc,silicon, or combinations thereof. For uniform dissolution of theprotective oxide coating to be attained, a component B is added to thealloy, possessing sufficient solubility in blood or interstitial fluid,such as lithium sodium, potassium, calcium, iron or manganese. Thecorrosion rate is adjusted by way of the composition so that gases, suchas hydrogen, which evolves during the corrosion of lithium, sodium,potassium, magnesium, calcium or zinc dissolve physically andessentially not forming any macroscopic gas bubbles. Other alloys can beutilized such as, for example, an alloy of lithium and magnesium in theratio of about 60:40; a sodium-magnesium alloy; zinc-titanium alloy—thepercentage by weight of which is in the range of about 0.1% to about 1%with gold being optionally added at a percentage by weight of about 0.1%to about 2%. Further details relating to these metallic bioabsorbablematerials are described in U.S. Pat. No. 6,287,332 to Bolz et al., whichis incorporated herein by reference in its entirety.

Other materials for either the stent framework or the connectors caninclude biodegradable polymers such as polylactic acid (i.e., PLA),polyglycolic acid (i.e., PGA), polydioxanone (i.e., PDS),polyhydroxybutyrate (i.e., PHB), polyhydroxyvalerate (i.e., PHV), andcopolymers or a combination of PHB and PHV (available commercially asBiopol®), polycaprolactone (available as Capronor®), polyanhydrides(aliphatic polyanhydrides in the back bone or side chains or aromaticpolyanhydrides with benzene in the side chain), polyorthoesters,polyaminoacids (e.g., poly-L-lysine, polyglutamic acid),pseudo-polyaminoacids (e.g., with back bone of polyaminoacids altered),polycyanocrylates, or polyphosphazenes. As used herein, the term“bio-resorbable” includes a suitable biocompatible material, mixture ofmaterials or partial components of materials being degraded into othergenerally non-toxic materials by an agent present in biological tissue(i.e., being bio-degradable via a suitable mechanism, such as, forexample, hydrolysis) or being removed by cellular activity (i.e.,bioresorption, bioabsorption, or bio-resorbable), by bulk or surfacedegradation (i.e., bioerosion such as, for example, by utilizing a waterinsoluble polymer that is soluble in water upon contact with biologicaltissue or fluid), or a combination of one or more of the bio-degradable,bio-erodable, or bio-resorbable material noted above.

The stent 100 can be made by various techniques. One technique isdescribed with reference to FIGS. 5A-5C. In FIG. 5A, a hollow generallytubular tube stock 40 of a suitable material (e.g., Nitinol or Elgiloy)is illustrated as having a portion 42′ of the tube stock 40 removed toprovide at least one opening 42 and preferably a plurality of openings.The opening 42 is partly covered by a bio-resorbable metallic plug 44that can be coupled to the tube stock 40, as illustrated in FIG. 5B. Inthe preferred embodiment, the plug 44 is a resorbable metal plug smallerthan the opening 42. At this point, the plug 44 is bonded to the tubestock 40 by a suitable brazing, heating, welding, or soldering processthat joins the plug 44 to the edges of the opening 42. Where the tubestock 40 is Nitinol, the joining process can be utilized by the oneshown and described in U.S. Pat. No. 5,242,759, which is incorporated byreference in its entirety herein. Thereafter, the tube stock 40 is cutto form a helical stent 100 in an unexpanded configuration where thehelical stent 100 outside diameter is smaller than the expandedconfiguration.

The process to join the metallic plug 44 involves applying to thesurface of the tube stock 40 a suitable flux having an activationtemperature below a predetermined annealing temperature of the tubestock 40. The activated flux has a composition of ingredients suitablefor removing contaminants from the surface of the tube stock 40 and forfurther removing at least portions of the titanium from the surfacewhile leaving the nickel therein. The flux with the contaminants and atleast portions of titanium suspended therein are removed from the tubestock 40 surface while leaving nickel to form a nickel-rich interfacesurface for bonding to another metal layer such as a solder material. Asa result, a low temperature solder material can flow on the nickel-richinterface surface to form a good metallic bond without affecting theshape memory or superelastic properties of the tube stock 40. Theremoval of contaminants can include at least partially leaching titaniumfrom the tube stock 40 alloy surface with the flux heated to itsactivation temperature then cooling the flux to form a solid coating ofthe flux on the nickel-rich interface surface after the flux-heating. Tostrengthen the metallic bond, the flux is scrubbed from the alloy membersurface to remove the suspended contaminants and titanium from thenickel-rich interface surface. Additional flux is applied to thescrubbed nickel-rich interface surface to leach additional titanium andto remove any remaining contaminants or oxidation. A metal such as atin-silver solder material is flowed to the nickel-rich interfacesurface of the tube stock 40 to displace from the interface surface thecoating of flux with the contaminant and titanium suspended therein. Anyremaining residual flux is then cleaned from the alloy member surfaceafter the application of the solder material thereto. Basic surfacepreparation is made to both the tube stock 40 and the plug 44. Then amolten solder having a melting point below a predetermined annealingtemperature of the tube stock 40 is applied to the nickel-rich interfacesurface. The plug 44 is positioned in contact with the molten solder,and cooling the molten solder to join the tube stock 40 to the plug 44.The flux utilized can be an aluminum flux paste having at least one oftin chloride, zinc chloride, hydrofluoric acid, ethanolamine, andcombination thereof as active ingredients. The solders utilized in thesoldering method can be selected from the group of gold, nickel, indium,tin, silver, cadmium, lead, zirconium, hafnium, and combinationsthereof. The soft solder is preferably a material with a meltingtemperature below about 425 degrees Celsius such as, for example, silversolder.

After the tube stock 40 has been joined with plug 44 to form a one-pieceunitary member 46 (with a portion of the member 44 illustrated in FIG.5C), the unitary member 46 is cut by a suitable cutting technique, suchas, for example, laser cutting, electro-discharge-machining, etching, asis known to those skilled in the art, one of which is shown anddescribed in U.S. Pat. No. 6,572,647, which is incorporated by referenceherein.

In the cutting process of FIG. 5C, the unitary member 46 is cutaccording to the design illustrate in FIG. 1, for example, with portionsdelineated by hatched lines indicating an example portion of thematerial removed in the cutting process. In particular, the cutting ofthe tube stock 40 is designed so that the portion forming the connector20 between the undulations U1 and U2 coincides with the resorbable plug44, shown with dashed lines in FIG. 5C.

Another technique to form a resorbable connector other than a metal(which is dissimilar to the tube stock 40 and which may be resorbable ornon-resorbable) can be as follows. A tube stock 40 (illustrated in FIG.5A) has an opening 42 formed therein by a suitable machining process.Instead of joining a resorbable metal to the opening 42, as illustratedin FIG. 5B, the struts S1-S4 are cut into the tube stock 40 asillustrated in FIG. 5D with the opening 42 present in the surface of thetube stock 40. To facilitate a connection between the undulations,vestiges 22A and 22B of the connector 20 can be provided. After thecutting and suitable surface preparation, a suitable non-metallicmaterial (including non-resorbable material but is preferablyresorbable) such as those described above and others known to thoseskilled in the art can be used to connect the connector vestiges 22A and22B together (with suitable geometry such as, for example, barbs, hooks,or flares to facilitate adherence to a non-metallic connector). Thenon-metallic resorbable material preferably is a polymer with sufficientstrength to form a connection between the undulations that can enduredelivery and implantation in a mammalian host for an acceptable periodof time before resorption by the host. In one embodiment, bio-activeagents can be added to the polymer or to the metal alloy for delivery tothe host's vessel or duct. The bio-active agents may also be used tocoat the entire stent. A coating may include one or more non-genetictherapeutic agents, genetic materials and cells and combinations thereofas well as other polymeric coatings.

Non-genetic therapeutic agents include anti-thrombogenic agents such asheparin, heparin derivatives, urokinase, and PPack (dextrophenylalanineproline arginine chloromethylketone); antiproliferative agents such asenoxaprin, angiopeptin, or monoclonal antibodies capable of blockingsmooth muscle cell proliferation, hirudin, and acetylsalicylic acid;anti-inflammatory agents such as dexamethasone, prednisolone,corticosterone, budesonide, estrogen, sulfasalazine, and mesalamine;antineoplastic/antiproliferative/anti-miotic agents such as paclitaxel,5-fluorouracil, cisplatin, vinblastine, vincristine, epothilones,endostatin, angiostatin and thymidine kinase inhibitors; anestheticagents such as lidocaine, bupivacaine, and ropivacaine; anti-coagulants,an RGD peptide-containing compound, heparin, antithrombin compounds,platelet receptor antagonists, anti-thrombin anticodies, anti-plateletreceptor antibodies, aspirin, prostaglandin inhibitors, plateletinhibitors and tick antiplatelet peptides; vascular cell growthpromotors such as growth factor inhibitors, growth factor receptorantagonists, transcriptional activators, and translational promotors;vascular cell growth inhibitors such as growth factor inhibitors, growthfactor receptor antagonists, transcriptional repressors, translationalrepressors, replication inhibitors, inhibitory antibodies, antibodiesdirected against growth factors, bifunctional molecules consisting of agrowth factor and a cytotoxin, bifunctional molecules consisting of anantibody and a cytotoxin; cholesterol-lowering agents; vasodilatingagents; and agents which interfere with endogenous vascoactivemechanisms.

Genetic materials include anti-sense DNA and RNA, DNA coding for,anti-sense RNA, tRNA or rRNA to replace defective or deficientendogenous molecules, angiogenic factors including growth factors suchas acidic and basic fibroblast growth factors, vascular endothelialgrowth factor, epidermal growth factor, transforming growth factor alphaand beta, platelet-derived endothelial growth factor, platelet-derivedgrowth factor, tumor necrosis factor alpha, hepatocyte growth factor andinsulin like growth factor, cell cycle inhibitors including CDinhibitors, thymidine kinase (“TK”) and other agents useful forinterfering with cell proliferation the family of bone morphogenicproteins (“BMPs”), BMP-2, BMP-3, BMP-4, BMP-5, BMP-6 (Vgr-1), BMP-7(OP-I), BMP-8, BMP-9, BMP-IO, BMP-I, BMP-12, BMP-13, BMP-14, BMP-15, andBMP-16. Desirable BMPs are any of BMP-2, BMP-3, BMP-4, BMP-5, BMP-6 andBMP-7. These dimeric proteins can be provided as homodimers,heterodimers, or combinations thereof, alone or together with othermolecules. Alternatively or, in addition, molecules capable of inducingan upstream or downstream effect of a BMP can be provided. Suchmolecules include any of the “hedgehog” proteins, or the DNA encodingthem.

Cells can be of human origin (autologous or allogeneic) or from ananimal source (xenogeneic), genetically engineered if desired to deliverproteins of interest at the deployment site. The cells may be providedin a delivery media. The delivery media may be formulated as needed tomaintain cell function and viability.

Suitable polymer coating materials include polycarboxylic acids,cellulosic polymers, including cellulose acetate and cellulose nitrate,gelatin, polyvinylpyrrolidone, cross-linked polyvinylpyrrolidone,polyanhydrides including maleic anhydride polymers, polyamides,polyvinyl alcohols, copolymers of vinyl monomers such as EVA, polyvinylethers, polyvinyl aromatics, polyethylene oxides, glycosaminoglycans,polysaccharides, polyesters including polyethylene terephthalate,polyacrylamides, polyethers, polyether sulfone, polycarbonate,polyalkylenes including polypropylene, polyethylene and high molecularweight polyethylene, halogenated polyalkylenes includingpolytetrafluoroethylene, polyurethanes, polyorthoesters, proteins,polypeptides, silicones, siloxane polymers, polylactic acid,polyglycolic acid, polycaprolactone, polyhydroxybutyrate valerate andblends and copolymers thereof, coatings from polymer dispersions such aspolyurethane dispersions (for example, BAYHDROL® fibrin, collagen andderivatives thereof, polysaccharides such as celluloses, starches,dextrans, alginates and derivatives, hyaluronic acid, squaleneemulsions. Polyacrylic acid, available as HYDROPLUS® (Boston ScientificCorporation, Natick, Mass.), and described in U.S. Pat. No. 5,091,205,the disclosure of which is hereby incorporated herein by reference, isparticularly desirable. Even more desirable is a copolymer of polylacticacid and polycaprolactone.

The preferred stents may also be used as the framework for a vasculargraft. Suitable coverings include nylon, collagen, PTFE and expandedPTFE, polyethylene terephthalate and KEVLAR®, ultra-high molecularweight polyethylene, or any of the materials disclosed in U.S. Pat. No.5,824,046 and U.S. Pat. No. 5,755,770, which are incorporated byreference herein. More generally, any known graft material may be usedincluding synthetic polymers such as polyethylene, polypropylene,polyurethane, polyglycolic acid, polyesters, polyamides, their mixtures,blends and copolymers.

In the preferred embodiments, some or all of the connectors arebio-resorbed while leaving the undulating strut configurationessentially unchanged. In other embodiments, however, the entire helicalstent can be resorbed in stages by a suitable coating over theresorbable material. For example, the connectors can resorb within ashort time period after implantation, such as, for example, 30 days. Theremaining helical stent framework (made of a resorbable material such asmetal or polymers) can thereafter resorb in a subsequent time period,such as, for example, 90 days to 2 years from implantation. For example,in the design graphically illustrated in FIG. 6, a stent 200 has an endsection ES with arcuate sections AS1-AS4 continuing on to another end ofthe stent 200 (not shown) (as with FIGS. 1 and 2, the continuous helicalpath of the arcuate sections AS is not shown for clarity). In someapplications, the use of the end section ES may facilitate crimping ofthe stent 200 into a loading device. In such situation, the end sectionES is connected to the helical arcuate sections AS1-AS4 via anon-resorbable material 30, preferably the same material as theundulations. The remainders of the arcuate sections that form thehelical configuration are coupled to each other via a resorbableconnector 20.

One technique of controlling the period of time after delivery that thearcuate sections or connector remain covered, and therefore not subjectto resorption or degradation, can be provided by using a suitablematerial that changes chemical structure upon exposure to a particularactivating wavelength of radiation (e.g., UV or visible light). In oneembodiment, the bio-resorbable structure (the struts or connector) isprovided with a water repellant coating that prevents body fluids fromdegrading the resorbable material. Once exposed to the activatingwavelength of radiation, the water repellant coating dissolves orbecomes porous so that hydrolytic or enzymatic degradation of theunderlying resorbable material can begin. In another example, exposureto a specific wavelength of light causes the light-activated material tochange structure to thereby allow separation between the cover materialand the underlying resorbable material. In an example, the activatingradiation can be UV light, visible light or near infrared laser light ata suitable wavelength (e.g., 800 nanometers) at which tissues aresubstantially transparent. In a particular embodiment, the coatingmaterial may be polyethylene with a melting point of about 60 degreesCelsius mixed with biocompatible dyes that absorb radiation in the 800nm range. Such dye can be Indocyanine green, which is a dye that absorbsradiation around 800 nm and is biocompatible, and will absorb the lightenergy and thereby raise the temperature in the polymer to about 60degrees Celsius or higher. Upon attainment of the melting pointtemperature, the polymer structurally weakens thereby allowing thecoating to lose integrity (i.e., crack, peal or otherwise become porousor at least a portion of the surface) thereby allowing biological fluidto come into contact with the underlying resorbable material andinitiate the resorption process. It is noted that the embodiment wherethe underlying stent framework and connectors are of a resorbablematerial, the stent framework and connectors would eventually resorbwithin a specified time period due to natural degradation of thecoating. The technique described herein, however, allows foracceleration of the resorption or degradation process.

As also illustrated in FIG. 6, markers M1 and M2 can be provided for allof the embodiments described herein. The marker M1 can be formed fromthe same material as the stent 200 as long as the material isradiographic or radiopaque. The marker material can also be formed fromgold, tantalum, platinum for example. The marker M1 can be formed from amarker material different from the marker M2.

The devices described herein can be, with appropriate modifications,delivered to an implantation site in a host with the delivery devicesdescribed and shown in U.S. Patent Application Publication Nos.2005/0090890 or 2002/0183826, U.S. Pat. No. 6,939,352 or 6,866,669,which are incorporated by reference herein in their entirety.

The design of the preferred embodiments is believed to be advantageousover the known partially bio-resorbable stent rings in that, where allof the connectors are designed to be resorbed, there is only oneremaining structure in the vessel or duct of the host. In contrast, withthe known partially resorbable stent rings, once all of the connectorsare resorbed in tissue, there is a multiplicity of separate ringsunconnected to each other, each of which can migrate.

It is believed that another possible problem that may arise with thepartially biodegradable ring stent is that, once the connectors haveresorbed in the body, the stent becomes a collection of discrete annularrings in the vessel or duct. As illustrated in FIG. 7, such separaterings R1 and R2, when distorted or compressed by an external force (suchas pressing on the carotid artery where such stent is implanted orsimply due to compression of the vessel or duct from body, jointmovements or muscle movements). As such each ring may be twisted into aconfiguration where the rings are no longer co-axial with the duct orvessel BV. This problem is illustrated in FIG. 7 where the axis AX ofone of the rings R1 is oblique to the longitudinal axis LX of the vesselor duct BV. Once the ring R1 is in this position, it is believed thatthe ring can no longer recover to its original coaxial position as ringR2. Thus, it is believed that this situation could potentially lead to apartial occlusion of the vessel.

Thus, the helical stent 100 and the various embodiments (with someembodiments more preferable than others) provide the ability to resistmigration in the host vessel or duct in the event that the connectorsbetween helical segments are absorbed before tissue ingrowth of the hostvessel is able to securely retain the stent to the host's vessel.Additionally, the preferred embodiments alleviate the possible problemof ring stent occluding a vessel when the ring is moved or contorted(e.g., by an external force such as compression or by the movement ofthe host's joints or muscles). Further, the use of at least one helixwith a small amount of connectors (e.g., in the situation where not allof the connectors are bio-resorbable) or no connectors allows forenhanced flexibility while implanted in the host.

Moreover, it is believed that the various embodiments allow for anunexpected advantage in that the flexibility of the preferred stents canbe configured to change subsequent to implantation in a biological ductor vessel either pre-configured in the stent or changed subsequently bya clinician. That is, the resorbable connectors permit the stent to havea first spring constant in an unimplanted condition and a seconddifferent spring constant in an implanted condition after apredetermined period of time or after the resorption of the stent orconnector is accelerated by an energy device external to the host. Inthe preferred embodiments, the first spring constant is preferably ahigher spring constant so as to maintain a desired axial spacing L1, L2,L3, and L4 generally constant (as illustrated in FIG. 4), which isbelieved to prevent intrusion or substantial prolapse of the biologicaltissue in between the axial spacing. The spring constant or spring ratecan be changed subsequently as part of the stent's initial configurationor via an agent (e.g., UV light or laser light) external of the host.

Although the various embodiments have been described in relation to aframework that define essentially a portion of a tube using wire likemembers, other variations are within the scope of the invention. Forexample, other embodiments of the framework may define differentcylindrical sections with different outer diameter; the framework maydefine a cylindrical section coupled to a conic section; the frameworkmay define a single cone; the wire-like members may be in cross-sectionsother than circular such as, for example, rectangular, square, orpolygonal.

While the present invention has been disclosed with reference to certainembodiments, numerous modifications, alterations, and changes to thedescribed embodiments are possible without departing from the sphere andscope of the present invention, as defined in the appended claims.Accordingly, it is intended that the present invention not be limited tothe described embodiments, but that it has the full scope defined by thelanguage of the following claims, and equivalents thereof.

1. A stent comprising: a plurality of arcuate sections circumscribing alongitudinal axis from a first portion to a second portion to define aportion of a tube, the plurality of arcuate sections spaced apart alongthe longitudinal axis to form at least one continuous helical path aboutthe longitudinal axis, the plurality of arcuate sections have anunexpanded insertion size and a larger expanded size, each arcuatesection including a plurality of struts that extend in differentdirections with respect to the longitudinal axis; and at least oneconnector connecting one of the plurality of struts of one arcuatesection to one of the plurality of struts of an axially spaced adjacentarcuate section, the at least one connector made from a material that isbioresorbed upon exposure to biological tissue such that the stent has afirst spring constant in an unimplanted condition and a different secondspring constant in an implanted condition after a predetermined periodof time.
 2. The stent according to claim 1, wherein a peak and a troughis arranged between three individual struts of the plurality of struts.3. The stent according to claim 2, wherein the at least one connectorconnects a peak of the one arcuate section to a peak of the adjacentarcuate section.
 4. The stent according to claim 2, wherein the at leastone connector connects a peak of the one arcuate section to a trough ofthe adjacent arcuate section.
 5. The stent according to claim 1, whereinthe at least one connector extends obliquely with respect to thelongitudinal axis.
 6. The stent according to claim 1, wherein the atleast one connector is formed of three generally linear segments suchthat the connector extends in three directions that are each not obliqueto the longitudinal axis.
 7. The stent according to claim 1, wherein theat least one connector is curvilinear along a length thereof.
 8. Thestent according to claim 1, wherein the at least one connector has awave-like shape along a length thereof.
 9. The stent according to claim1, further including a plurality of connectors connecting adjacentarcuate sections, about 30% or about 50% of a total number of theplurality of connectors being the at least one connector.
 10. A helicalstent comprising: a plurality of arcuate sections circumscribing alongitudinal axis from a first portion to a second portion to define aportion of a tube, the plurality of arcuate sections spaced apart alongthe longitudinal axis to form a portion of at least one continuoushelical path about the longitudinal axis; and at least one connectorconnecting one arcuate section to an adjacent arcuate section, the atleast one connector made of a material that is absorbed upon exposure tobiological tissue.
 11. The helical stent according to claim 10, whereina plurality of struts of the one arcuate section and a plurality ofstruts of the adjacent arcuate section include pairs of struts thattogether form an apex, the at least one connector connecting an apex ofthe one arcuate section to an apex of the adjacent arcuate section. 12.The helical stent according to claim 11, wherein the at least oneconnector extends obliquely with respect to the longitudinal axis. 13.The helical stent according to claim 11, wherein the at least oneconnector is formed of three generally linear segments such that theconnector extends in three directions that are each not oblique to thelongitudinal axis.
 14. The stent according to claim 11, wherein the atleast one connector is curvilinear along a length thereof.
 15. A stentcomprising: a plurality of arcuate sections circumscribing alongitudinal axis from a first portion to a second portion to define aportion of a tube, the arcuate sections being spaced apart along thelongitudinal axis to form at least one continuous helical path about thelongitudinal axis such that the stent has a first spring constant in anunimplanted condition and a second different spring constant in animplanted condition after a predetermined period of time.
 16. The stentaccording to claim 15, wherein at least one connector connects onearcuate section to an adjacent arcuate section, the at least oneconnector made of a material that is absorbed upon exposure tobiological tissue.
 17. The stent according to claim 16, wherein aplurality of arcuate struts of the one arcuate section and a pluralityof struts of the adjacent arcuate section include pairs of struts thatare coupled together via a curved intermediate member that forms anapex, the at least one connector connecting an apex of the one arcuatesection to an apex of the adjacent arcuate section.
 18. The stentaccording to claim 17, wherein the at least one connector extendsobliquely with respect to the longitudinal axis.
 19. The stent accordingto claim 17, wherein the at least one connector is formed of threegenerally linear segments such that the connector extends in threedirections that are each not oblique to the longitudinal axis.
 20. Thestent according to claim 17, wherein the at least one connector iscurvilinear along a length thereof.